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Targeting, Attacking, Eradicating Cancer

JX-929

Targeting, Attacking, Eradicating Cancer

JX929 is an engineered vaccinia virus strain that acts on cancer cells both by viral attack and subsequent cancer cell lysis ("oncolysis"). JX-929 utilizes the Western Reserve strain of oncolytic vaccinia virus. To optimize tumor selectivity, the viral genes for both thymidine kinase (TK) and vaccinia growth factor (VGF) were disrupted. In nonclinical studies, the JX-929 backbone exerted a tumor debulking effect and at the same time demonstrated a selective preference for tumor tissues (Thorne et al., Journal of Clinical Investigation 2007
(http://www.ncbi.nlm.nih.gov/pubmed/17965776)).

Further, JX-929 was also designed to activate chemotherapy specifically in cancer tissue. The hope is that selective activation of chemotherapy in cancer tissue may decrease side effects and increase potency. JX929 was engineered to express the prodrugactivating enzyme (cytosine deaminase) that could convert a subsequently administered nontoxic prodrug 5-fluorocytosine (5-FC) to its cytotoxic drug form 5-fluorouracil (5FU). In theory, because of the virus’s tumor selectivity, production of the cytotoxic drug would be concentrated at the site of the tumor, minimizing side effects on normal tissues and enhancing efficacy against the tumor. In a preclinical study, combination therapy of JX929 administered with the prodrug 5-FC showed a survival benefit compared to either therapy alone (Chalikonda et al., Cancer Gene Therapy 2008 (http://www.ncbi.nlm.nih.gov/pubmed/18084242)).

JX929 has been administered as a monotherapy to patients with breast, colorectal, and pancreatic cancer via intratumoral & intravenous injections in a Phase 1, doseescalation clinical trial. To date, results of this clinical trial show delivery to and replication within tumors (Zeh et al., Molecular Therapy 2015
(http://www.ncbi.nlm.nih.gov/pubmed/25292189)).

  • BaselineBaseline
  • Day 8Day 8
  • Day 75Day 75

JX929 in melanoma.
Tumor response was observed as tumorspecific ulceration, leaving intervening skin unaffected. The tumor scabbed over by Day 22 (not shown) and completely healed by Day 75 (Molecular Therapy 2015).

  • Pre-treatment Pre-treatment
  • Day 28Day 28

JX929 in metastatic colon cancer.
CT scans reveal tumor necrosis and inflammation of a metastatic mass after injection with JX 929 (Molecular Therapy 2015).